TY - JOUR
T1 - Proteomic analysis of serum in workers exposed to diesel engine exhaust
AU - Rahman, Mohammad L.
AU - Bassig, Bryan A.
AU - Dai, Yufei
AU - Hu, Wei
AU - Wong, Jason Y.Y.
AU - Blechter, Batel
AU - Hosgood, H. Dean
AU - Ren, Danzhi
AU - Duan, Huawei
AU - Niu, Yong
AU - Xu, Jun
AU - Fu, Wei
AU - Meliefste, Kees
AU - Zhou, Baosen
AU - Yang, Jufang
AU - Ye, Meng
AU - Jia, Xiaowei
AU - Meng, Tao
AU - Bin, Ping
AU - Silverman, Debra T.
AU - Vermeulen, Roel
AU - Rothman, Nathaniel
AU - Zheng, Yuxin
AU - Lan, Qing
N1 - Funding Information:
The Center for Human Immunology (CHI), NIH Clinical Center generated proteomics data used in this analysis. This work was supported by intramural funds from the National Cancer Institute and the National Institutes of Health, and the Key Program of National Natural Science Foundation of China (Grant no. NSFC 81130050).
Funding Information:
Key Program of National Natural Science Foundation of China, Grant/Award Number: NSFC 81130050; National Cancer Institute, National Institutes of Health, Grant/Award Number: Intramural grant Funding information
Publisher Copyright:
© 2021 Environmental Mutagen Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
PY - 2022/1
Y1 - 2022/1
N2 - Diesel engine exhaust (DEE) is classified as a Group 1 human carcinogen. Using a targeted proteomics approach, we aimed to identify proteins associated with DEE and characterize these markers to understand the mechanisms of DEE-induced carcinogenicity. In this cross-sectional molecular epidemiology study, we measured elemental carbon (EC) using a personal air monitor and quantified 1317 targeted proteins in the serum using the SOMAScan assay (SOMALogic) among 19 diesel exposed factory workers and 19 unexposed controls. We used linear regressions to identify proteins associated with DEE and examined their exposure-response relationship across levels of EC using linear trend tests. We further examined pathway enrichment of DEE-related proteins using MetaCore. Occupational exposure to DEE was associated with altered levels of 22 serum proteins (permutation p <.01). Of these, 13 proteins (CXCL11, HAPLN1, FLT4, CD40LG, PES1, IGHE.IGK.IGL, TNFSF9, PGD, NAGK, CCL25, CCL4L1, PDXK, and PLA2G1B) showed an exposure-response relationship with EC (p trend <.01), with serum levels of all but PLA2G1B declining with increasing air levels of EC. For instance, C-X-C Motif Chemokine Ligand 11 (CXCL11) showed the most significant association with DEE (β = −0.25; permutation p =.00004), where mean serum levels were 4121.1, 2356.7, and 2298.8 relative fluorescent units among the unexposed, lower exposed (median, range : 56.9, 40.2–62.1 μg/m3 EC), and higher exposed (median, range of EC: 72.9, 66.9–107.7 μg/m3 EC) groups, respectively (p trend =.0005). Pathway analysis suggested that these proteins are enriched in pathways related to inflammation and immune regulation. Our study suggests that DEE exposure is associated with altered serum proteins, which play a role in inflammation and immune regulation.
AB - Diesel engine exhaust (DEE) is classified as a Group 1 human carcinogen. Using a targeted proteomics approach, we aimed to identify proteins associated with DEE and characterize these markers to understand the mechanisms of DEE-induced carcinogenicity. In this cross-sectional molecular epidemiology study, we measured elemental carbon (EC) using a personal air monitor and quantified 1317 targeted proteins in the serum using the SOMAScan assay (SOMALogic) among 19 diesel exposed factory workers and 19 unexposed controls. We used linear regressions to identify proteins associated with DEE and examined their exposure-response relationship across levels of EC using linear trend tests. We further examined pathway enrichment of DEE-related proteins using MetaCore. Occupational exposure to DEE was associated with altered levels of 22 serum proteins (permutation p <.01). Of these, 13 proteins (CXCL11, HAPLN1, FLT4, CD40LG, PES1, IGHE.IGK.IGL, TNFSF9, PGD, NAGK, CCL25, CCL4L1, PDXK, and PLA2G1B) showed an exposure-response relationship with EC (p trend <.01), with serum levels of all but PLA2G1B declining with increasing air levels of EC. For instance, C-X-C Motif Chemokine Ligand 11 (CXCL11) showed the most significant association with DEE (β = −0.25; permutation p =.00004), where mean serum levels were 4121.1, 2356.7, and 2298.8 relative fluorescent units among the unexposed, lower exposed (median, range : 56.9, 40.2–62.1 μg/m3 EC), and higher exposed (median, range of EC: 72.9, 66.9–107.7 μg/m3 EC) groups, respectively (p trend =.0005). Pathway analysis suggested that these proteins are enriched in pathways related to inflammation and immune regulation. Our study suggests that DEE exposure is associated with altered serum proteins, which play a role in inflammation and immune regulation.
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U2 - 10.1002/em.22469
DO - 10.1002/em.22469
M3 - Article
C2 - 34894159
AN - SCOPUS:85122003324
SN - 0893-6692
VL - 63
SP - 18
EP - 28
JO - Environmental and Molecular Mutagenesis
JF - Environmental and Molecular Mutagenesis
IS - 1
ER -